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Lernmark, Å.* ; Agardh, D.* ; Akolkar, B.* ; Gesualdo, P.* ; Hagopian, W.A.* ; Haller, M.J.* ; Hyöty, H.* ; Johnson, S.B.* ; Larsson, H.E.* ; Liu, E.* ; Lynch, K.F.* ; McKinney, E.F.* ; McIndoe, R.* ; Melin, J.* ; Norris, J.M.* ; Rewers, M.* ; Rich, S.S.* ; Toppari, J.* ; Triplett, E.W.* ; Vehik, K.* ; Virtanen, S.M.* ; Ziegler, A.-G. ; Schatz, D.A.* ; Krischer, J.*

Looking back at the TEDDY study: Lessons and future directions.

Nat. Rev. Endocrinol., DOI: 10.1038/s41574-024-01045-0 (2024)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The goal of the TEDDY (The Environmental Determinants of Diabetes in the Young) study is to elucidate factors leading to the initiation of islet autoimmunity (first primary outcome) and those related to progression to type 1 diabetes mellitus (T1DM; second primary outcome). This Review outlines the key findings so far, particularly related to the first primary outcome. The background, history and organization of the study are discussed. Recruitment and follow-up (from age 4 months to 15 years) of 8,667 children showed high retention and compliance. End points of the presence of autoantibodies against insulin, GAD65, IA-2 and ZnT8 revealed the HLA-associated early appearance of insulin autoantibodies (1-3 years of age) and the later appearance of GAD65 autoantibodies. Competing autoantibodies against tissue transglutaminase (marking coeliac disease autoimmunity) also appeared early (2-4 years). Genetic and environmental factors, including enterovirus infection and gastroenteritis, support mechanistic differences underlying one phenotype of autoimmunity against insulin and another against GAD65. Infant growth and both probiotics and high protein intake affect the two phenotypes differently, as do serious life events during pregnancy. As the end of the TEDDY sampling phase is approaching, major omics approaches are in progress to further dissect the mechanisms that might explain the two possible endotypes of T1DM.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Korrespondenzautor
Schlagwörter Diabetes-associated Autoantibodies; Celiac-disease Autoimmunity; Hydrolyzed Infant Formula; Hl-a Antigens; Islet Autoimmunity; Environmental Determinants; Genetic Risk; Young Teddy; Respiratory-infections; Rising Incidence
ISSN (print) / ISBN 1759-5029
e-ISSN 1759-5037
Verlag Nature Publishing Group
Verlagsort New York, NY
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Förderungen
University of Colorado
NIH/NCATS Clinical and Translational Science Awards to the University of Florida
JDRF
Centers for Disease Control and Prevention (CDC)
National Institute of Environmental Health Sciences (NIEHS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Diabetes and Digestive and Kidney diseases (NIDDK)